Pharmacokinetic models are developed for the distribution and disposition of drugs, environmental contaminants, and endogenous metabolites in animals and humans. They provide a plausible set of equations that can be used to extrapolate data from animals to humans, and thereby improve chemotherapy and risk assessment. Consideration of regional drug delivery includes intra-arterial infusion, intracavitary administration, and direct intratumoral infusion. Work is well advanced on the development of a physiological pharmacokinetic model for methylmercury and inorganic mercury in the rat. Emphasis has been placed on the pharmacokinetics of macromolecules such as monoclonal antibodies and immunotoxins. Preclinical and Phase I pharmacology have been completed on immunotoxin injected into the CSF. Pharmacokinetics of alkylating agents used in cancer therapy provide a basis for correlating interspecies carcinogenicity.